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Biomedical subjects

Y Guo

Publications and source records attributed to Y Guo.

At least 577 records · Page 32Linked to original sources

[Detection of vaginal and cervical human papillomavirus by electronic microscope examination and polymerase chain reaction technique].

UNLABELLED: Forty-seven specimens, biopsied during April-July 1990, pathologically proven to be vaginal or cervical condyloma acuminata (CA) in 34, wart-like lesions in 6, infections in 7, were screened for detection of human papillomavirus (HPV) by electronic microscope (EM) examination and polymerase chain reaction (PCR) technique. HPV type 11 (HPV-11) infections were diagnosed by Dot-blot hybridization in 40 out of these 47 specimens. RESULTS: (1) No typical virus particles was observed in all samples under EM examinations. However, interchromatin and perichromatin granules were found within the nuclei of koilocytes in 88.23% of the vaginal CA specimens. Nuclear bodies were seen in 3 out of 27 vaginal CA and HPV11 positive specimens. Furthermore, koilocytosis was also seen in the basal and parabasal layers of vaginal mucosa. (2) The positive rate for detection of HPV11 and HPV6 DNA by PCR technique in vaginal CA specimens was 92.6%, while positive rate for HPV 11, 6, 16 and 18 DNA was only 3.7%.

Adult↗

[Effects of moxibustion on the function of MDR gene product, P-glycoprotein (P-170)].

The experiments were performed on BABL/c mice with S-180R adriamycin resistant tumor cells. This animal model was used to analyze the drug accumulation in the S-180R cells by flow cytometer. The drug accumulation presents the pump activity of multidrug resistance (MDR) gene product P-glycoprotein (P-170) in the cell membrane, A weak inhibition was found when moxibustion at Guan-Yan point alone. And a very significant inhibition was observed in the presence of low-dosage of verapamil, but not at high dose. This study may develop a new way to research the mechanism of acupuncture and moxibustion at molecular level, and may be useful to overcome the anticancer drug resistance.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Congenital lower lip sinuses].

Congenital lower sinuses are rare and are found often in association with cleft lip and/or palate, named Van der Woude syndrome. Although the condition per se does not always require surgical attention, its genetic character is interesting. Four cases of congenital sinuses are described and recent literature is reviewed.

Abnormalities, Multiple↗

[Study on genetic epidemiology of albinism].

Segregation analysis and consanguinity analysis were applied to 37 albinism families ascertained from Shandong province (P. R. China) to study the genetic heterogeneity of the disease. Our results show that albinism is an autosomal recessive disease with multilocus. The least number of the detrimental loci is 8, The average frequence of detrimental genes is 0.0023, and 3.83% individuals in general population are carriers. The incidence among the offsprings of the first cousin marriages would be 22 times higher than that in the general population.

Albinism↗

A major costimulatory molecule on antigen-presenting cells, CTLA4 ligand A, is distinct from B7.

CTLA4 ligands are important costimulatory molecules because soluble CTLA4Ig blocks the induction of T cell responses and induces T cell tolerance. As CTLA4 immunoglobulin (CTLA4Ig) binds B7 when the latter is expressed on fibroblasts, it was widely assumed that CTLA4Ig blocks T cell costimulation by blocking the function of B7. Here we show that the major costimulatory ligand bound by CTLA4Ig (which we term CTLA4 ligand A) on antigen-presenting cells are not encoded by the B7 gene. CTLA4 ligand A also differs from B7 in cellular distribution and in the respective levels of expression. Both B7 and CTLA4 ligand A are critically involved in T cell costimulation.

Abatacept↗

Regulation of biosynthesis of the basic fibroblast growth factor binding domains of heparan sulfate by heparan sulfate-N-deacetylase/N-sulfotransferase expression.

Heparan sulfate-N-deacetylase/N-sulfotransferase catalyzes both the N-deacetylation and N-sulfation reactions that initiate the modification of the oligosaccharide backbone of heparan sulfate (HS). The glycosaminoglycan polymer appears to modulate the activity of growth factors by mediating their initial binding. To understand how the biosynthesis of these binding sites is regulated, a rat liver-derived cDNA encoding the above activities was overexpressed in a COS cell mutant (CM-15) that has reduced levels of the enzyme and binds poorly to immobilized basic fibroblast growth factor (bFGF). This resulted in increased synthesis of sulfated blocks of decasaccharide size or longer. These blocks exhibited high affinity binding to bFGF and contained a high content of 2-O-sulfated iduronate and at least five consecutive N-sulfated disaccharides. An increase in the synthesis of these high affinity blocks was not seen in transfected wild-type COS cells even though they showed a 4-fold increase of both enzyme activities, suggesting that once sufficient levels of highly sulfated blocks of saccharides with high affinity for bFGF are attained, no further synthesis of these domains occurs.

Amidohydrolases↗

Smith-Fineman-Myers syndrome: report on a large family.

Smith-Fineman-Myers syndrome is considered an X-linked mental retardation (XLMR) syndrome. Three families have been reported to date. However, none presented a typical pattern of X-linked inheritance. Here we reported on 5 males with Smith-Fineman-Myers syndrome with similar phenotypic expression as in those cases reported previously; they were distributed in 4 sibships of one large maternal kindred. This finding adds strong support to the hypothesis of the Smith-Fineman-Myers syndrome being a rare XLMR syndrome.

Child↗

Anti-CD3:anti-IL-2 receptor bispecific monoclonal antibody. Targeting of activated T cells in vitro.

T cells are major mediators of graft rejection and many autoimmune diseases. During the Ag recognition process, T cells often become activated. We tested the hypothesis that an anti-CD3:anti-CD25 (CD3,25) bispecific mAb (BSMAB) can effectively and selectively target activated T cells. By flow cytometric analysis, the CD3,25 BSMAB was shown to bind avidly to activated T cells that coexpress CD3 and CD25 (p55 chain of the IL-2R), achieving higher levels than the parent anti-CD3 and anti-CD25 mAb. It bound only weakly to unstimulated T cells. The CD3,25 BSMAB effectively redirected CTL to lyse CD25-bearing PHA-stimulated T lymphoblasts and the IL2-dependent CTLL tumor cell line in chromium release assays. It was highly effective in blocking MLR as shown by inhibition of [3H]TdR incorporation. However, the CD3,25 BSMAB has a low potential to activate resting T cells, as it induced only minimal [3H]TdR incorporation even in the presence of exogenous IL-2. In the absence of exogenous IL-2, the CD3,25 BSMAB was unable to induce [3H]TdR incorporation. In contrast, the parent anti-CD3 mAb induced a high degree of incorporation. In summary, the CD3,25 BSMAB selectively targets activated CD25-expressing T cells and lymphomas although maintaining a low activation potential for unstimulated T cells, potentially advantageous properties that can be exploited for immunotherapy.

Animals↗

Production of intracellular enzyme by Corynebacterium glutamicum T6-13 protoplasts immobilized in Ca-alginate gels.

The glutamate dehydrogenase (GDH) (EC 1.4.1.4) productivity of the immobilized Corynebacterium glutamicum T6-13 protoplasts in Ca-alginate gels was investigated. GDH in Corynebacterium glutamicum T6-13 cells is an intracellular enzyme. The cells pretreated with 0.5 U/l-1 penicillin G were used for the preparation of protoplasts. Protoplasts were prepared by treating these cells with lysozyme at 30 degrees C for 14 h in 0.5 M NaCl solution and separating the protoplasts. Protoplasts were directly immobilized in 3% Ca-alginate gels (method I). The immobilized protoplasts could be also prepared by treating the immobilized whole cells with lysozyme (method II); this method was more convenient than method I. The GDH productivity of the immobilized protoplasts amounted to 205% of that of the free cells (intracellular). The immobilized protoplasts could be repeatedly used for at least 6 batches (18 days) and had good storage stability.

Alginates↗

Acquired amegakaryocytic thrombocytopenic purpura with a Philadelphia chromosome.

A 30-year-old Chinese man with acquired amegakaryocytic thrombocytopenic purpura (AATP) and a Ph chromosome is reported. At presentation, he had severe thrombocytopenia resulting in epistaxis, gingival bleeding, and ecchymoses, while other hematologic values were within the normal range. Bone marrow aspiration showed no megakaryocytes, with a normal appearance of erythroblastic and granulopoietic series. He failed to respond to prednisone treatment, and underwent a progress from isolated thrombocytopenia to full pancytopenia. At last he died of spontaneous intracranial hemorrhage. An in vitro culture for granulocyte-macrophage precursors showed very few colonies. Karyotypic analysis revealed a standard Ph chromosome translocation, t(9;22)(q34;q11), in the majority of bone marrow cells. Southern blot analysis using a 3' bcr-HE probe didn't detect a rearrangement within the bcr DNA sequence. This patient, in fact, was a myelodysplastic disorder, initially presenting as AATP. The diagnosis of chronic myelogenous leukemia was excluded on the basis of clinical and hematologic findings. The heterogeneity of Ph chromosome in myelodysplastic syndrome is discussed.

Adult↗

Divalent cation competition with [3H]saxitoxin binding to tetrodotoxin-resistant and -sensitive sodium channels. A two-site structural model of ion/toxin interaction.

Monovalent and divalent cations competitively displace tetrodotoxin and saxitoxin (STX) from their binding sites on nerve and skeletal muscle Na channels. Recent studies of cloned cardiac (toxin-resistant) and brain (toxin-sensitive) Na channels suggest important structural differences in their toxin and divalent cation binding sites. We used a partially purified preparation of sheep cardiac Na channels to compare monovalent and divalent cation competition and pH dependence of binding of [3H]STX between these toxin-resistant channels and toxin-sensitive channels in membranes prepared from rat brain. The effects of several chemical modifiers of amino acid groups were also compared. Toxin competition curves for Na+ in heart and Cd2+ in brain yielded similar KD values to measurements of equilibrium binding curves. The monovalent cation sequence for effectiveness of [3H]STX competition is the same for cardiac and brain Na channels, with similar KI values for each ion and slopes of -1. The effectiveness sequence corresponds to unhydrated ion radii. For seven divalent cations tested (Ca2+, Mg2+, Mn2+, Co2+, Ni2+, Cd2+, and Zn2+) the sequence for [3H]STX competition was also similar. However, whereas all ions displaced [3H]STX from cardiac Na channels at lower concentrations, Cd2+ and Zn2+ did so at much lower concentrations. In addition, and by way of explication, the divalent ion competition curves for both brain and cardiac channels (except for Cd2+ and Zn2+ in heart and Zn2+ in brain) had slopes of less than -1, consistent with more than one interaction site. Two-site curves had statistically better fits than one-site curves. The derived values of KI for the higher affinity sites were similar between the channel types, but the lower affinity KI's were larger for heart. On the other hand, the slopes of competition curves for Cd2+ and Zn2+ were close to -1, as if the cardiac Na channel had one dominant site of interaction or more than one site with similar values for KI. pH titration of [3H]STX binding to cardiac channels showed a pKa of 5.5 and a slope of 0.6-0.9, compared with a pKa of 5.1 and slope of 1 for brain channels. Tetramethyloxonium (TMO) treatment abolished [3H]STX binding to cardiac and brain channels and STX protected channels, but the TMO effect was less dramatic for cardiac channels. Trinitrobenzene sulfonate preferentially abolished [3H]STX binding to brain channels by action at an STX protected site.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effects of combined iodine and selenium deficiency on thyroid hormone metabolism in rats.

This paper compares the effects of combined iodine and selenium deficiency, of single deficiencies of these trace elements, and of no deficiency on thyroid hormone metabolism in rats. In rats deficient in both trace elements, thyroidal triiodothyronine (T3), thyroidal thyroxin (T4), thyroidal total iodine, hepatic T4, and plasma T4 were significantly lower, and plasma thyroid-stimulating hormone (TSH) and thyroid weight were significantly higher than in rats deficient in iodine alone. Plasma and hepatic T3 concentrations were similar in the dietary groups. Hepatic type I iodothyronine deiodinase (ID-I) activity was inhibited by selenium deficiency irrespective of the iodine status. Type II deiodinase (ID-II) activity in the brain was significantly higher and in pituitary, significantly lower in combined deficiency than in iodine deficiency alone. These data show that selenium can play an important role in determining the severity of the hypothyroidism associated with iodine deficiency.

Animals↗

Selective impairment of the synthesis of basic fibroblast growth factor binding domains of heparan sulphate in a COS cell mutant defective in N-sulphotransferase.

N-Sulphation is a key step in the overall sulphation of heparan sulphate. We have isolated a COS cell-derived mutant, CM-15, that is impaired in its ability to bind to basic fibroblast growth factor (bFGF) and has a 2- to 3-fold reduction in N-sulphotransferase activity [Ishihara et al., (1992a) Anal. Biochem., 206, 400-407]. We now provide structural evidence that CM-15 is selectively impaired in the synthesis of highly sulphated regions or 'blocks' that display high-affinity binding to bFGF; these are completely N-sulphated blocks of decasaccharide or greater length that are enriched in O-sulphate groups. The synthesis of sulphated blocks that did not show high affinity to the growth factor was relatively unimpaired in the mutant cells; this included fully N-sulphated octamer (or smaller) blocks and, unexpectedly, decasaccharide or larger blocks that were poorly O-sulphated. In the latter fraction, the failure to form high-affinity binding regions was the result of a failure to stimulate O-sulphation rather than N-sulphation in CM-15 cells. In agreement with other studies, disaccharide analysis of the wild-type-derived sulphated blocks suggested that 2-O-sulphation of iduronate residues in the polymer was a necessary element to produce a high-affinity binding sequence once N-sulphation was completed in the decasaccharide or larger fraction. These results suggest that a selective reduction in both N- and O-sulphation in the larger blocks produced by CM-15 cells is a consequence of the reduction of N-sulphotransferase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗

Development of specific antibodies to rat insulin-like growth factor-binding proteins (IGFBP-2 to -6): analysis of IGFBP production by rat granulosa cells.

Six insulin-like growth factor-binding proteins (IGFBPs) have been isolated and their cDNAs cloned in the rat and human species. The next step is to develop antibodies to each IGFBP. Toward this goal, we generated rabbit polyclonal antibodies to rat IGFBP-2, -4, -5, and -6, using synthetic peptide fragments of the IGFBPs. A rat IGFBP-3 polyclonal antibody was prepared in a previous study using the native protein. Western immunoblotting demonstrated that the IGFBP-2, -3, -4, -5, and -6 antibodies were highly specific for their respective antigens. The elicited antisera were used to study IGFBP production in primary cultures of rat granulosa cells grown in serum-free medium for 72 h. Ligand blotting with 125I-labeled IGF-I and IGF-II revealed two bands migrating at 29 and 24 kilodaltons (kDa) in the medium of untreated control cells, whereas no bands were detectable in medium from cells incubated with 100 ng/ml FSH. Western blotting of control medium with all of the IGFBP antibodies revealed that the IGFBP-4 antibody stained two bands at 28 and 24 kDa, and the IGFBP-5 antibody stained two bands at 30 and 29 kDa. By contrast, these bands were absent in medium from FSH-stimulated cells; instead, two lower molecular mass bands of 21.5 and 17.5 kDa were detected with the IGFBP-4 antibody, and a 21-kDa band was seen with the IGFBP-5 antibody. The same 21.5- and 17.5-kDa bands were seen when exogenously added IGFBP-4 was incubated with the FSH-conditioned medium, whereas untreated medium did not degrade the added IGFBP-4. Incubation with the conditioned medium also degraded exogenous IGFBP-5 to yield a 21-kDa band. By contrast, medium from control cells did not degrade the exogenous IGFBP-5. This finding indicates that FSH induced the production of a protease from granulosa cells that degraded IGFBP-4 and -5 in the culture medium. No IGFBPs were detectable in medium from control or FSH-treated cells using the IGFBP-2, -3, and -6 antibodies. Northern blotting analysis of the same control granulosa cell cultures revealed a 2.6-kilobase and a 6.0-kilobase transcript for IGFBP-4 and -5, respectively; however, the IGFBP-4 and -5 mRNAs were essentially undetectable in FSH-treated cell cultures. To determine the effects of the IGFBPs on steroidogenesis, dose-response experiments were performed with IGFBP-4 and -5.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Increased follistatin (activin-binding protein) gene expression in rat anterior pituitary tissue after ovariectomy may be mediated by pituitary activin.

For lack of evidence to the contrary, it is now believed that the FSH-suppressing actions of follistatin are due to its ability to bind endogenous pituitary activin. Recent data have demonstrated a role for pituitary activin-B in mediating FSH hypersecretion after ovariectomy (OVX) and during the secondary FSH surge on estrus. Therefore, given that follistatin is produced within anterior pituitary tissue, and considering the potentially important function of follistatin to modulate activin bioactivity, we sought to gain insights into the regulation of follistatin gene expression in the anterior pituitary gland of adult female rats. At the termination of all in vivo investigations, rats were killed, trunk blood was collected for determination of serum LH and FSH levels by RIA, and pituitary tissue was collected, pooled (two or three glands per pool), and processed for determination of follistatin messenger RNA (mRNA) levels by a solution-hybridization RNase protection assay. In the first experiment, pituitary follistatin mRNA levels were significantly (P < 0.01) increased 3 weeks after OVX. Treatment of long-term ovariectomized rats with a Nal-Glu LHRH antagonist restored serum LH levels to precastration levels and suppressed serum FSH concentrations by 70%, but follistatin message levels were not altered. In contrast, treatment of castrated rats with recombinant human follistatin-288 selectively suppressed serum FSH levels (50%) and completely abolished OVX-induced increases in follistatin mRNA levels. Subsequent experiments revealed that OVX-induced increases in follistatin gene expression could be observed in pituitary tissue grafted underneath the kidney capsule of hypophysectomized rats. Furthermore, follistatin mRNA levels were significantly (P < 0.05) higher in pituitary glands taken from estrous rats during the secondary FSH surge (0200 h) than in glands obtained from rats on proestrous morning when serum FSH levels were basal. Because increased steady state follistatin mRNA levels in the latter two instances were associated with selective FSH hypersecretion, and such hypersecretion was previously shown to be dependent to a significant degree on pituitary activin, we next tested the hypothesis that increased pituitary follistatin gene expression is mediated by activin. Using cultures of dispersed pituitary cells, addition of recombinant human activin-A for 72 h increased follistatin mRNA levels 3-fold while enhancing only FSH secretion. Collectively, the present results demonstrate a coupling of follistatin gene expression in the anterior pituitary gland with changes in pituitary FSH secretion under conditions where LH secretion is unaltered. Viewed in the context of previous work, the data also suggest that changes in follistatin mRNA levels may be linked to activin signaling.

Activins↗